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Abstract：
Evolutionary change in gene regulation is a key mechanism underlying the genetic component of organismal diversity. Here, we study evolution of regulation at the posttranslational level by examining the evolution of cyclin-dependent kinase (CDK) consensus phosphorylation sites in the protein subunits of the pre-replicative complex (RC). The pre-RC, an assembly of proteins formed during an early stage of DNA replication, is believed to be regulated by CDKs throughout the animals and fungi. Interestingly, although orthologous pre-RC components often contain clusters of CDK consensus sites, the positions and numbers of sites do not seem conserved. By analyzing protein sequences from both distantly and closely related species, we confirm that consensus sites can turn over rapidly even when the local cluster of sites is preserved, consistent with the notion that precise positioning of phosphorylation events is not required for regulation. We also identify evolutionary changes in the clusters of sites and further examine one replication protein, Mcm3, where a cluster of consensus sites near a nucleocytoplasmic transport signal is confined to a specific lineage. We show that the presence or absence of the cluster of sites in different species is associated with differential regulation of the transport signal. These findings suggest that the CDK regulation of MCM nuclear localization was acquired in the lineage leading to Saccharomyces cerevisiae after the divergence with Candida albicans. Our results begin to explore the dynamics of regulatory evolution at the posttranslational level and show interesting similarities to recent observations of regulatory evolution at the level of transcription.
摘要：
基因调控的进化变化是生物体多样性遗传成分的关键机制。这里,我们通过检查前复制复合物(RC)蛋白质亚基中细胞周期蛋白依赖性激酶(CDK)共有磷酸化位点的进化,来研究翻译后水平的调控进化.前RC，在DNA复制的早期阶段形成的蛋白质集合，被认为在整个动物和真菌中被CDK调节。有趣的是,尽管直系同源前RC成分通常包含CDK共识位点簇，网站的位置和数量似乎并不保守。通过分析来自远缘和密切相关物种的蛋白质序列，我们确认，即使保留了本地站点集群，共识站点也可以迅速翻转，与磷酸化事件的精确定位不是调节所必需的概念一致。我们还确定了位点簇的进化变化，并进一步检查了一种复制蛋白，Mcm3，其中核质转运信号附近的一组共有位点仅限于特定谱系。我们表明，不同物种中位点簇的存在或不存在与运输信号的差异调节有关。这些发现表明，MCM核定位的CDK调节是在与白色念珠菌分歧后导致酿酒酵母的谱系中获得的。我们的结果开始探索翻译后水平的调控进化的动力学，并显示出与最近在转录水平上的调控进化观察的有趣相似性。
